This is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study of orally administered lomitapide in healthy male Japanese and Caucasian subjects with elevated LDL-C. The purpose for this study is to evaluate the PK and PD of lomitapide in Japanese subjects as compared to Caucasian subjects.

A Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics(PK) and Pharmacodynamics(PD) of Lomitapide in Japanese and Caucasian Volunteers With Elevated Low-density-lipoprotein(LDL-C)

Pharmacokinetics (PK) comparison [ Time Frame: Pharmacokinetic samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ] [ Designated as safety issue: No ]

To compare the pharmacokinetics (PK) of lomitapide between Japanese and Caucasian subjects with elevated LDL-C after single and multiple doses, across the dose range studied.

Secondary Outcome Measures:

To evaluate the number of adverse events and changes in laboratory parameters in order to assess safety of lomitapide in Japanese and Caucasian subjects with elevated LDL-C. [ Time Frame: Samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ] [ Designated as safety issue: Yes ]

To assess the single dose and multiple dose safety of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.

To evaluate the number of adverse events and changes in laboratory parameters in order to assess tolerability in Japanese and Caucasian subjects with elevated LDL-C. [ Time Frame: Samples will be taken pre-dose on Day 1 up to Day 27 post treatment ] [ Designated as safety issue: No ]

To assess the single dose and multiple dose tolerability of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.

To evaluate the number of adverse events and changes in laboratory parameters in order to assess pharmacodynamics(PD)of lomitapide in Japanese and Caucasian subjects with elevated LDL-C. [ Time Frame: Samples will be taken pre-dose on Day 1 up to Day 27 post treatment. ] [ Designated as safety issue: No ]

To assess the pharmacodynamic(PD) of lomitapide in Japanese and Caucasian subjects with elevated LDL-C.

3. Subjects must have a screening LDL-C measurement and the mean of Day 5 and Day 6 measurements greater than or equal to 120mg/dL.

4. Subjects must agree to use acceptable methods of contraception (details provided in the protocol)

5. Subjects must be capable of understanding and complying with the requirements of the protocol and must have signed the informed consent form prior to undergoing any study-related procedures.

Exclusion Criteria:

Subject has a clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion.

Any clinically significant abnormal laboratory, vital signs or other safety findings as determined by medical history, physical examination or other evaluations conducted at screening or on admission.

Electrocardiogram (ECG) abnormalities in the standard 12-lead ECG (at screening) which in the opinion of the Investigator is clinically relevant or will interfere with the ECG analysis.

History or current evidence of any clinically relevant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological, psychiatric or other disease.

Confirmed positive results from urine drug screen or from the alcohol breath test at screening and on admission (Day -1).

History or clinical evidence of alcohol or drug abuse.

Mentally handicapped.

Participation in a drug trial within 90 days prior to first drug administration.

Use of any medication (including over-the-counter (OTC) medication) within 2 weeks prior to admission (Day -1) or within less than 10 times the elimination half-life of the respective drug, or anticipated concomitant medication during the treatment periods.

Use of any substance inhibiting CYP3A4 enzymes within 2 weeks prior to admission (Day -1).

Donation of more than 500 mL of blood within 90 days prior to drug administration.

Subjects who smoke more than 10 cigarettes or equivalent amount of tobacco per day and/or who cannot stop smoking for the duration of the study whilst in the CPU.

Treatment with herbal supplements during the 7 days prior to dosing, or use of vitamins during 48 hours prior to admission (Day -1).

Any circumstances or conditions, which, in the opinion of the PI, may affect full participation in the trial or compliance with the protocol.

Legal incapacity or limited legal capacity at screening.

Subjects who are vegetarians, vegans or have any dietary restrictions conflicting with the study standardised menus.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01760187